Oxidative Stress, Mitochondrial Dysfunction, and Aβ Pathology: Converging Pathways in Aging and Neurodegeneration

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 2051

Editors


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Guest Editor
Department of Neurology, McKnight Brain Institute, and Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL 32611, USA
Interests: aging; oxidative stress; neurodegeneration; Drosophila; C. elegans

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Guest Editor
Department of Aging and Physiology, Institute on Aging, University of Florida, Gainesville, FL 32610, USA
Interests: aging; mitochondrial biology; toxicology; oxidative stress; C. elegans

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Guest Editor
Department of Infectious Disease and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA
Interests: regulated cell death; cell signaling; mitochondrial biogenesis; pharmaceutical

Special Issue Information

Dear Colleagues,

This Special Issue highlights cutting-edge research in oxidative stress and mitochondrial biology, with a particular focus on their roles in aging, regulated cell death, and neurodegenerative conditions, including amyloid-β (Aβ) pathology.

Oxidative stress arises from imbalanced levels of reactive oxygen and nitrogen species (RONS), which serve as key modulators of physiological processes such as host defense, apoptosis, and cellular senescence. Both endogenous and exogenous sources contribute to reactive and non-reactive oxidative stress.

Mitochondria are central to RONS generation, functioning within the electron transport chain (ETC) to drive ATP production via oxidative phosphorylation (OXPHOS). While RONS are essential signaling molecules, their dysregulation leads to inflammatory damage, apoptosis, and tissue degeneration. These disruptions accelerate aging, contribute to Aβ accumulation and aggregation, and promote the progression of neurodegenerative diseases including Alzheimer's disease.

Recent studies have advanced our understanding of oxidative stress regulation, mitochondrial dynamics, and Aβ-associated pathology, paving the way for novel therapeutic strategies and standardized management protocols. This Special Issue welcomes original research and review articles that explore oxidative stress mitigation, mitochondrial function, and molecular mechanisms in the context of aging, neurodegeneration, and regulated cell death pathways.

Dr. Swapnil Pandey
Dr. Laxmi Rathor
Dr. Ashish Shukla
Guest Editors

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Keywords

  • oxidative stress
  • aging
  • amyloid beta
  • tau phosphorylation
  • neurodegeneration
  • regulated cell death
  • mitochondrial biogenesis
  • Drosophila
  • C. elegans

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Published Papers (1 paper)

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Review

26 pages, 1942 KB  
Review
Microbiota–Gut–Brain Axis in Alzheimer’s Disease: Linking Oxidative Stress, Mitochondrial Dysfunction and Amyloid Pathology—A Systematic Review
by Shah Rezlan Shajahan, Nurhidayah Hamid, Blaire Okunsai, Norshafarina Shari and Muhammad Danial Che Ramli
Biomedicines 2026, 14(4), 860; https://doi.org/10.3390/biomedicines14040860 - 9 Apr 2026
Cited by 1 | Viewed by 1649
Abstract
Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β aggregation, tau hyperphosphorylation, oxidative stress, and mitochondrial dysfunction. Emerging evidence indicates that the gut microbiota plays a critical role in modulating neuroinflammatory, and metabolic pathways involved in AD pathogenesis through the [...] Read more.
Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β aggregation, tau hyperphosphorylation, oxidative stress, and mitochondrial dysfunction. Emerging evidence indicates that the gut microbiota plays a critical role in modulating neuroinflammatory, and metabolic pathways involved in AD pathogenesis through the microbiota-gut-brain axis. Objective: This systematic review aims to comprehensively evaluate the role of the microbiota-gut-brain axis in Alzheimer’s disease, with a particular focus on its mechanistic links to oxidative stress, mitochondrial dysfunction, and amyloid pathology, as well as its therapeutic potential. Methodology: A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases, focusing on studies evaluating gut microbiota composition, metabolomic changes, oxidative stress markers, mitochondrial activity, and therapeutic interventions in AD models and patients. Results: Altered gut microbial composition in AD is associated with increased pro-inflammatory taxa (Escherichia-Shigella, Bacteroides) and depletion of short-chain fatty acid (SCFA) producing bacteria (Faecalibacterium, Roseburia). Dysbiosis contributes to systemic inflammation, disrupted intestinal permeability, and microglial activation, leading to oxidative damage and mitochondrial impairment in neurons. Preclinical and clinical studies indicate that probiotics, prebiotics, and fecal microbiota transplantation can restore redox balance, reduce neuroinflammation, and improve cognitive outcomes. Multi-omics and AI-based models are emerging as tools for identifying microbiome-derived biomarkers for early AD detection. Conclusion: The gut microbiota-mitochondria-oxidative stress axis represents a promising therapeutic target in Alzheimer’s disease. Future research should focus on longitudinal human studies, standardized microbial profiling, and personalized microbiome-based interventions to translate these mechanistic insights into clinical benefit. Full article
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